DESCRIPTION (applicant's abstract): Obesity is a disease of literally and figuratively enormous proportions. A model of naturally occurring obesity, photoperiod-induced seasonal obesity in Siberian hamsters, was chosen for study. Siberian hamsters are naturally obese when housed in long "summer-like" days. This obesity gradually develops and is expressed fully when the animals are adults. When Siberian hamsters are exposed to short days, as in fall/winter, they lose body fat. With subsequent increasing day lengths, as occurs in spring/summer, they regain their body fat; thus, the obesity is reversible, unlike most of the animal models of human obesity. It seems that a better understanding of the fundamental processes involved in the development and reversal of obesity might result from studying this natural cycle of body fat because, in these animals, it is seasonally advantageous for them to be obese at one time of year and lean at another time of the year. Two aspects of the control of fatness are the focus of this grant proposal: 1) the connections of the brain to body fat by the sympathetic nervous system, and 2) the regulation of total body fat as revealed by the compensatory increases in fat that are triggered after surgically-produced decreases in fatness (lipectomy). Attempts will be made to identify a brain controller of the number of fat cells in the body, including the chemical means by which the brain communicates with fat depots to increase or decrease fat cell number. Further attempts will be made to identify how the brain "knows" when body fat is decreased after we remove some of it experimentally (lipectomy). Tests will be done directly to one brain area, the paraventricular nucleus, to determine whether it is involved in the control of the short-day-induced decreases in fatness, as seems to be suggested by the neural circuitry connecting this brain area to body fat. Finally, a new strategy/tactic will be used to identify the chemicals in the brain that are part of the neural circuit connecting the brain to fat and that may be involved in the reversal from obese to the lean state. This multidisciplinary approach should provide new information about the importance of the control of body fat by the brain. In addition, these findings should provide insight into the fundamental processes involved in the development, maintenance, and especially the reversal of obesity.